It has been called the golden elixir of life. It still holds much information for those who know how to look for it. The most cost-effective device used to screen urine is a paper or plastic dipstick. This microchemistry system has been available for many years and allows qualitative and semi-quantitative analysis within one minute by simple but careful observation. The color change occurring on each segment of the strip is compared to a color chart to obtain results.
METHODS OF URINE COLLECTION
Taken at any time of day with no precautions regarding contamination. The sample may be dilute, isotonic, or hypertonic and may contain white cells, bacteria, and squamous epithelium as contaminants.
In females, the specimen may contain vaginal contaminants such as trichomonads, yeast, and during menses, red cells.
Early morning Early morning collection of the sample before ingestion of any fluid. This is usually hypertonic and reflects the ability of the kidney to concentrate urine during dehydration which occurs overnight. If all fluid ingestion has been avoided since 6 p.m. the previous day, the specific gravity usually exceeds 1.022 in healthy individuals. Mid stream Clean catch
Collected after cleansing the external urethral meatus. A cotton sponge soaked with benzalkonium hydrochloride is useful and non-irritating for this purpose.
First half of the bladder urine is discarded and the collection vessel is introduced into the urinary stream to catch the last half
First half of the stream serves to flush contaminating cells and microbes from the outer urethra prior to collection
Catheterization of the bladder
Only in special circumstances, i.e., in a comatose or confused patient
Risks introducing infection and traumatizing the urethra and bladder, producing iatrogenic infection or hematuria.
Suprapubic transabdominal needle aspiration of the bladder Provides the purest sampling of bladder urine
Good method for infants and small children.
Normal, fresh urine is pale to dark yellow or amber in color
A red or red-brown (abnormal) color could be from a food dye, eating fresh beets, a drug, or the presence of either hemoglobin or myoglobin. If the sample contained many red blood cells, it would be cloudy as well as red.
Volume 750 to 2000 ml/24hr Clarity Turbidity or cloudiness may be caused by excessive cellular material or protein in the urine or may develop from crystallization or precipitation of salts upon standing at room temperature or in the refrigerator. Clearing of the specimen after addition of a small amount of acid indicates that precipitation of salts is the probable cause of tubidity
URINE DIPSTICK CHEMICAL ANALYSIS
pH The glomerular filtrate of blood plasma is usually acidified by renal tubules and collecting ducts from a pH of 7.4 to about 6 in the final urine. However, depending on the acid-base status, urinary pH may range from as low as 4.5 to as high as 8.0. The change to the acid side of 7.4 is accomplished in the distal convoluted tubule and the collecting duct. Specific gravity
Any specific gravity > 1.022 measured in a randomly collected specimen denotes adequate renal concentration so long as there are no abnormal solutes in the urine. (which is directly proportional to urine osmolality which measures solute concentration) measures urine density, or the ability of the kidney to concentrate or dilute the urine over that of plasma.
Dipsticks are available that also measure specific gravity in approximations. Most laboratories measure specific gravity with a refractometer. Specific gravity between 1.002 and 1.035 on a random sample should be considered normal if kidney function is normal. Since the sp gr of the glomerular filtrate in Bowman's space ranges from 1.007 to 1.010, any measurement below this range indicates hydration and any measurement above it indicates relative dehydration. If sp gr is not > 1.022 after a 12 hour period without food or water, renal concentrating ability is impaired and the patient either has generalized renal impairment or nephrogenic diabetes insipidus. In end-stage renal disease, sp gr tends to become 1.007 to 1.010.
Any urine having a specific gravity over 1.035 is either contaminated, contains very high levels of glucose, or the patient may have recently received high density radiopaque dyes intravenously for radiographic studies or low molecular weight dextran solutions. Subtract 0.004 for every 1% glucose to determine non-glucose solute concentration.
Screening for protein is done on whole urine, but semi-quantitative tests for urine protein should be performed on the supernatant of centrifuged urine since the cells suspended in normal urine can produce a falsely high estimation of protein.
Normally, only small plasma proteins filtered at the glomerulus are reabsorbed by the renal tubule. However, a small amount of filtered plasma proteins and protein secreted by the nephron (Tamm-Horsfall protein) can be found in normal urine. Normal total protein excretion does not usually exceed 150 mg/24 hours or 10 mg/100 ml in any single specimen. More than 150 mg/day is defined as proteinuria. Proteinuria > 3.5 gm/24 hours is severe and known as nephrotic syndrome.
Dipsticks detect protein by production of color with an indicator dye, Bromphenol blue, which is most sensitive to albumin but detects globulins and Bence-Jones protein poorly. Precipitation by heat is a better semiquantitative method, but overall, it is not a highly sensitive test.
The sulfosalicylic acid test is a more sensitive precipitation test. It can detect albumin, globulins, and Bence-Jones protein at low concentrations. In rough terms, trace positive results (which represent a slightly hazy appearance in urine) are equivalent to 10 mg/100 ml or about 150 mg/24 hours (the upper limit of normal). 1+ corresponds to about 200-500 mg/24 hours, a 2+ to 0.5-1.5 gm/24 hours, a 3+ to 2-5 gm/24 hours, and a 4+ represents 7 gm/24 hours or greater.
Glucose Less than 0.1% of glucose normally filtered by the glomerulus appears in urine (< 130 mg/24 hr). Glycosuria (excess sugar in urine) generally means diabetes mellitus. Dipsticks employing the glucose oxidase reaction for screening are specific for glucos glucose but can miss other reducing sugars such as galactose and fructose. For this reason, most newborn and infant urines are routinely screened for reducing sugars by methods other than glucose oxidase (such as the Clinitest, a modified Benedict's copper reduction test). Ketones Ketones (acetone, aceotacetic acid, beta-hydroxybutyric acid) resulting from either diabetic ketosis or some other form of calorie deprivation (starvation), are easily detected using either dipsticks or test tablets containing sodium nitroprusside. Nitrite
A positive nitrite test indicates that bacteria may be present in significant numbers in urine.
Gram negative rods such as E. coli are more likely to give a positive test.
A positive leukocyte esterase test results from the presence of white blood cells either as whole cells or as lysed cells. Pyuria can be detected even if the urine sample contains damaged or lysed WBC's.
A negative leukocyte esterase test means that an infection is unlikely and that, without additional evidence of urinary tract infection, microscopic exam and/or urine culture need not be done to rule out significant bacteriuria
Urine is centrifuged in a test tube forming a cohesive button at the bottom of the tube. The sediment is resuspended in the remaining supernate and a drop of resuspended sediment is poured onto a glass slide and coverslipped. The sediment is first examined under the microscope at both low and high power.
Low power examination is used to determine the numbers of casts seen are usually reported as number of each type found per low power field (LPF). Example: 5-10 hyaline casts/L casts/LPF.
High power examination is used to identify crystals, cells, and bacteria. The various types of cells are usually described as the number of each type found per average high power field (HPF). Example: 1-5 WBC/HPF.
Red Blood Cells
Hematuria is the presence of abnormal numbers of red cells in urine due to: glomerular damage, tumors which erode the urinary tract anywhere along its length, kidney trauma, urinary tract stones, renal infarcts, acute tubular necrosis, upper and lower uri urinary tract infections, nephrotoxins, and physical stress.
Red cells may also contaminate the urine from the vagina in menstruating women or from trauma produced by bladder catherization. Theoretically, no red cells should be found, but some find their way into the urine even in very healthy individuals. However, if one or more red cells can be found in every high power field, and if contamination can be ruled out, the specimen is probably abnormal.
RBC's may appear normally shaped, swollen by dilute urine (in fact, only cell ghosts and free hemoglobin may remain), or crenated by concentrated urine. Both swollen, partly hemolyzed RBC's and crenated RBC's are sometimes difficult to distinguish from WBC's in the urine. In addition, red cell ghosts may simulate yeast. The presence of dysmorphic RBC's in urine suggests a glomerular disease such as a glomerulonephritis. Dysmorphic RBC's have odd shapes as a consequence of being distorted via passage through the abnormal glomerular structure.
White blood cells Pyuria refers to the presence of abnormal numbers of leukocytes that may appear with infection in either the upper or lower urinary tract or with acute glomerulonephritis. Usually, the WBC's are granulocytes. White cells from the vagina, especially in the presence of vaginal and cervical infections, or the external urethral meatus in men and women may contaminate the urine. If two or more leukocytes per each high power field appear in non-contaminated urine, the specimen is probably abnormal. Epithelial cells
Renal tubular epithelial cells, usually larger than granulocytes, contain a large round or oval nucleus and normally slough into the urine in small numbers.
However, with nephrotic syndrome and in conditions leading to tubular degeneration, the number sloughed is increased. When lipiduria occurs, these cells contain endogenous fats. When filled with numerous fat droplets, such cells are called oval fat bodies. Oval fat bodies exhibit a "Maltese cross" configuration by polarized light microscopy.
Transitional epithelial cells from the renal pelvis, ureter, or bladder have more regular cell borders, larger nuclei, and smaller overall size than squamous epithelium.
Renal tubular epithelial cells are smaller and rounder than transitional epithelium, and their nucleus occupies more of the total cell volume.
Squamous epithelial cells from the skin surface or from the outer urethra can appear in urine. Their significance is that they represent possible contamination of the specimen with skin flora.
Urinary casts are formed only in the distal convoluted tubule (DCT) or the collecting duct (distal nephron). The proximal convoluted tubule (PCT) and loop of Henle are not locations for cast formation.
Hyaline casts are composed primarily of a mucoprotein (Tamm-Horsfall protein) secreted by tubule cells. Even with glomerular injury causing increased glomerular permeability to plasma proteins with resulting proteinuria, most matrix or "glue" that cements urinary casts together is Tamm-Horsfall mucoprotein, although albumin and some globulins are also incorporated.
The factors which favor protein cast formation are low flow rate, high salt concentration, and low pH, all of which favor protein denaturation and precipitation, particularly that of the Tamm-Horsfall protein. Protein casts with long, thin tails formed at the junction of Henle's loop and the distal convoluted tubule are called cylindroids. Hyaline casts can be seen even in healthy patients.
Red blood cells may stick together and form red blood cell casts. Such casts are indicative of glomerulonephritis, with leakage of RBC's from glomeruli, or severe tubular damage.
White blood cell casts are most typical for acute pyelonephritis, but they may also be present with glomerulonephritis. Their presence indicates inflammation of the kidney, because such casts will not form except in the kidney.
When cellular casts remain in the nephron for some time before they are flushed into the bladder urine, the cells may degenerate to become a coarsely granular cast, later a finely granular cast, and ultimately, a waxy cast. Granular and waxy casts are be believed to derive from renal tubular cell casts.
Broad casts are believed to emanate from damaged and dilated tubules and are therefore seen in end-stage chronic renal disease.
The so-called telescoped urinary sediment is one in which red cells, white cells, oval fat bodies, and all types of casts are found in more or less equal profusion. The conditions which may lead to a telescoped sediment are: 1) lupus nephritis 2) malignant hypertension 3) diabetic glomerulosclerosis, and 4) rapidly progressive glomerulonephritis. In end-stage kidney disease of any cause, the urinary sediment often becomes very scant because few remaining nephrons produce dilute urine.
Bacteria are common in urine specimens because of the abundant normal microbial flora of the vagina or external urethral meatus and because of their ability to rapidly multiply in urine standing at room temperature. Therefore, microbial organisms found in all but the most scrupulously collected urines should be interpreted in view of clinical symptoms.
Diagnosis of bacteriuria in a case of suspected urinary tract infection requires culture. A colony count may also be done to see if significant numbers of bacteria are present. Generally, more than 100,000/ml of one organism reflects significant bacteriuria. Multiple organisms reflect contamination. However, the presence of any organism in catheterized or suprapubic tap specimens should be considered significant.
Yeast Yeast cells may be contaminants or represent a true yeast infection. They are often difficult to distinguish from red cells and amorphous crystals but are distinguished by their tendency to bud. Most often they are Candida, which may colonize bladder, urethra, or vagina Crystals
Common crystals seen even in healthy patients include calcium oxalate, triple phosphate crystals and amorphous phosphates.
Very uncommon crystals include: cystine crystals in urine of neonates with congenital cystinuria or severe liver disease, tyrosine crystals with congenital tyrosinosis or marked liver impairment, or leucine crystals in patients with severe liver disease or with maple syrup urine disease. Oxalate crystals in urine Triple phosphate crystals in urine Cystine crystals in urine
Miscellaneous Unidentifiable objects may find their way into a specimen, particularly those that patients bring from home.
Spermatozoa can sometimes be seen.
Rarely, pinworm ova may contaminate the urine.
In Egypt, ova from bladder infestations with schistosomiasis may be seen.
INTERFERING DISEASES OR SUBSTANCES CHARACTERIZATION Changes occurring if there is a time delay after collection to analysis
Generally, urinalysis may not reflect the findings of absolutely fresh urine if the sample is > 1 hour old
1) Decreased clarity due to crystallization of solutes
2) Rising pH
3) Loss of ketone bodies
4) Loss of bilirubin
5) Dissolution of cells and casts
6) Overgrowth of contaminating microorganisms
An unusual complication from a functioning indwelling urethral catheter: case report of an abdominal mass.
Keys RH Jr, Spreen SA, Evans AT.
J Urol 1976 Aug;116(2):257-8 Abstract quote
A heretofore unreported complication from an indwelling catheter is presented. A catheter bulb became incarcerated in a bladder diverticulum and was misdiagnosed subsequently as an incarcerated umbilical hernia. The probable pathophysiological mechanism by which this event occurred is discussed.
Catheter-related injuries as cause of acute surgical condition within abdomen.
Urology 1979 Mar;13(3):261-3 Abstract quote
Three cases of an acute surgical condition within the abdomen secondary to complications of chronic urethral catheters are reported. Common factors in the history and varying mechanisms for the injuries are discussed. Need for including catheter-related injuries in the differential diagnosis of an acute surgical condition of the abdomen is emphasized.
Peritonitis and abdominal free air due to intraperitoneal bladder perforation associated with indwelling urethral catheter drainage.
Merguerian PA, Erturk E, Hulbert WC Jr, Davis RS, May A, Cockett AT.
J Urol 1985 Oct;134(4):747-50 Abstract quote
Perforation of the bladder related to long-term indwelling Foley catheter drainage is a rare and serious complication.
We report 2 cases of bladder perforation leading to generalized peritonitis and free intraperitoneal air. These cases re-emphasize the importance of considering bladder perforation in the differential diagnosis of the acute abdomen and of performing a complete abdominal exploration when the site of perforation is not easily detectable.
Pressure ulcers: an unusual complication of indwelling urethral catheter.
Sivaraman Nair KP, Taly AB, Roopa N, Murali T.
Department of Psychiatric and Neurological Rehabilitation, National Institute of Mental Health and Neurosciences, Bangalore, India.
Spinal Cord 2001 Apr;39(4):234-6 Abstract quote
INTRODUCTION: Pressure ulcers are common among patients with spinal cord disorders (SCD) and occur due to unrelieved pressure on soft tissues.
CASE REPORTS: Two ladies with paraplegia following acute transverse myelitis developed pressure ulcers over medial aspects of thighs due to indwelling urethral catheter. Absence of sensation, weakness of both legs and lack of knowledge about catheter care contributed to ulcer formation.
CONCLUSION: Indwelling urethral catheter may unusually result in pressure ulcers over the thighs in patients with SCD. Among health professionals involved in the care of these subjects awareness is essential for preventing this complication.
Effect of a single-use sterile catheter for each void on the frequency of bacteriuria in children with neurogenic bladder on intermittent catheterization for bladder emptying.
Schlager TA, Clark M, Anderson S.
Department of Pediatrics, University of Virginia Health System, Charlottesville, Virginia.
Pediatrics 2001 Oct;108(4):E71 Abstract quote
The frequency of bacteriuria is high in children with neurogenic bladder on intermittent catheterization for bladder emptying. In an effort to decrease bacteriuria, we examined whether the method of catheter care was responsible for the high rate of bacteriuria. For this, the frequency of bacteriuria was examined in the same patient on single-use sterile catheters and on reused clean catheters.
Methods. A prospective, randomized, crossover trial was conducted with 10 patients who were randomized to 4 months of a new, sterile catheter for intermittent catheterization and 4 months of reuse of a clean catheter for intermittent catheterization. Each week, a urine sample was collected and symptoms of infection and medication use were recorded. Results. A total of 158 urine samples were collected during 164 patient-weeks on the new catheter method for each void; 115 (73%) were positive for a pathogen. Of the 161 samples collected during 169 patient-weeks on the standard, reuse method for voiding, 123 (76%) were positive (115 [73%] of 158 vs 123 [76%] of 161). Escherichia coli was the most common pathogen detected during both method periods.
Conclusion. A new, sterile catheter for each void did not decrease the high frequency of bacteriuria in patients with neurogenic bladder on intermittent catheterization.
Rapid Spot Tests for Detecting the Presence of Adulterants in Urine Specimens Submitted for Drug Testing
Amitava Dasgupta, PhD, Amer Wahed, MD, and Alice Wells, MT(ASCP)
Am J Clin Pathol 2002;117:325-329 Abstract quote
Several adulterants are used to mask tests for abused drugs in urine. Adulterants such as "Klear" and "Whizzies" contain potassium nitrite, and "Urine Luck" contains pyridinium chlorochromate (PCC). The presence of these adulterants cannot be detected by routine specimen integrity checks (pH, specific gravity, and temperature).
We developed rapid spot tests for detecting these adulterants in urine. Addition of 3% hydrogen peroxide in urine adulterated with PCC caused rapid formation of a dark brown color. In contrast, unadulterated urine turned colorless when hydrogen peroxide was added. When urine contaminated with nitrite and 2 to 3 drops of 2N hydrochloric acid were added to 2% aqueous potassium permanganate solution, the dark pink permanganate solution turned colorless immediately with effervescence. Urine contaminated with nitrite liberated iodine from potassium iodide solution in the presence of 2N hydrochloric acid. Urine adulterated with PCC also liberated iodine from potassium iodide in acid medium but did not turn potassium permanganate solution colorless. Urine specimens from volunteers and random urine samples that tested negative for drugs did not cause false-positive results.
These rapid spot tests are useful for detecting adulterated urine to avoid false-negative drug tests.
Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Twentieth Edition. WB Saunders. 2001.
Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 5th Edition. McGraw-Hill. 1999.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.
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